Nucleophilic addition of 3,3,3-trifluoropropynyllithium to d-glyceraldimine: Concise synthesis of both enantiomers of 5,5,5-trifluoronorvaline

3,3,3-Trifluoropropynyllithium, in situ generated by treatment of 2-bromo-3,3,3-trifluoro-1-propene 1 with 2.0 equiv. of LDA at −78 °C, was trapped with d-glyceraldimine 2 to give trifluoromethylated propargylic amine 4 in 55% yield. Starting from the key intermediate 4, Boc-protected (R)-5,5,5-trifluoronorvaline and (S)-5,5,5-trifluoronorvaline were concisely synthesized over three steps in 62% and 63% yield, respectively.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide